Radiolabeling, biodistribution and gamma scintigraphy of noscapine hydrochloride in normal and polycystic ovary induced rats.
Radiolabeling, biodistribution and gamma scintigraphy of noscapine hydrochloride in normal and polycystic ovary induced rats.
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DOI：
10.1186/1757-2215-3-10
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发表时间：
2010-04-27
影响因子：
4
通讯作者：
Bhatnagar A
中科院分区：
文献类型：
--
作者：
Priyadarshani A;Chuttani K;Mittal G;Bhatnagar A
诺斯卡品是一种来自罂粟的生物碱，广泛用作镇咳药，主要由于其抗血管生成特性，正在临床上研究用于治疗多囊卵巢综合征（PCOS）和其他一些癌症。随着诺斯卡品的不同应用的出现，我们试图确定放射性标记方法是否可用于研究体内分子的摄取和动力学。本研究的具体目的是用锝-99m（Tc-99 m）放射性标记诺斯卡品，测定其在大鼠模型中的器官生物分布，并研究其在PCOS模型中的摄取动力学。采用亚锡还原法建立了99 m Tc标记诺斯卡品的标准化方法，并研究了其体内外稳定性。还评价了放射性药物的血液动力学和生物分布特征。用抗孕酮剂RU 486建立PCOS动物模型，用γ射线显像比较正常和PCOS卵巢对~（99）mTc-诺斯卡品的摄取。盐酸诺斯卡品成功地被Tc-99 m标记，具有较高的标记效率和体外稳定性。大部分药物（80%）的血液清除发生在血管内注射后的第一个小时内，在肝、脾、肾中观察到最大蓄积，其次是卵巢。注射后4小时，与正常周期大鼠（0.53 ± 0.01%ID/整个器官）相比，大鼠PCOS卵巢中的放射性标记复合物蓄积加倍（0.9 ± 0.03%ID/整个器官）。在不同时间间隔（1 h、2 h、4 h和24 h）拍摄的大鼠SPECT图像进一步加强了这一观察结果，其中SPECT图像显示PCOS卵巢中的离散积累。通过我们的研究，我们报告了直接放射性标记的诺斯卡品和它的生物分布在不同的器官和特定的摄取PCOS，可能会显示其效用成像卵巢病理。PCOS患者卵巢摄取增加可能与其受体结合有关，提示99 mTc-诺斯卡品在PCOS诊断和治疗中可能发挥作用。
Noscapine, an alkaloid from Papaver somniferum, widely used as an antitussive, is being clinically studied in the treatment of polycystic ovary syndrome (PCOS) and a few other cancers primarily because of its anti-angiogenesis properties. With the advent of diverse application of noscapine, we sought to determine whether the radiolabeling method can be useful in studying uptake and kinetics of the molecule in-vivo. Specific objectives of this study were to radiolabel noscapine with Technetium-99m (Tc-99m), to determine its organ biodistribution in rat model and study its uptake kinetics in PCOS model. A method for radiolabeling noscapine with Tc-99m was standardized using stannous reduction method and its in vitro and in vivo stability parameters were studied. The radiopharmaceutical was also evaluated for blood kinetics and biodistribution profile. An animal model of PCOS was created by using antiprogesterone RU486 and uptake of 99mTc-noscapine in normal and PCOS ovaries was compared using gamma scintigraphy. Noscapine hydrochloride was successfully radiolabeled with Tc-99m with high labeling efficiency and in vitro stability. Most of the blood clearance of the drug (80%) took place in first hour after intravascular injection with maximum accumulation being observed in liver, spleen, kidney followed by the ovary. At 4 hours post injection, radiolabeled complex accumulation doubled in PCOS ovaries in rats (0.9 ± 0.03% ID/whole organ) compared to normal cyclic rats (0.53 ± 0.01% ID/whole organ). This observation was further strengthened by scintigraphic images of rats taken at different time intervals (1 h, 2 h, 4 h, and 24 h) where SPECT images suggested discrete accumulation in the PCOS ovaries. Through our study we report direct radiolabeling of noscapine and its biodistribution in various organs and specific uptake in PCOS that may show its utility for imaging ovarian pathology. The increased ovarian uptake in PCOS may be related to its receptor binding suggesting possible role of 99mTc-noscapine in PCOS diagnostics and therapeutics.
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影响因子：
3
作者：
Aneja, Ritu;Dhiman, Neerupma;Joshi, Harish C.
通讯作者：
Joshi, Harish C.
影响因子：
2.9
作者：
KARLSSON, MO;DAHLSTROM, B;ALM, AT
通讯作者：
ALM, AT
影响因子：
6.1
作者：
Ibáñez, L;Valls, C;de Zegher, F
通讯作者：
de Zegher, F
影响因子：
5.8
作者：
Ke, Y;Ye, K;Kapp, JA
通讯作者：
Kapp, JA
影响因子：
2.9
作者：
EMPEY, DW;LAITINEN, LA;HUGHES, DTD
通讯作者：
HUGHES, DTD